Prostate specific antigen (PSA), a well characterized tumor associated antigen, is a significant diagnostic and prognostic marker in human prostatic carcinoma. As prostate tumor cells release PSA into the bloodstream, PSA concentrations in serum and other body fluids correlate with the progression of primary or metastatic carcinoma. Accordingly, the quantitation of PSA in patient specimens provides clinicians with an effective means of monitoring a therapeutic regimen and evaluating remission or progression of the disease state.
Present immunoassays for the measurement of PSA in patient fluid samples, such as the immunoradiometric assay (IRMA) and the enzyme-linked immunosorbent assay (ELISA), rely on the use of artificial or synthetic matrices, such as bovine serum albumin, as calibrator matrices and as diluents. As used herein, the term "calibrator matrix" refers to a matrix in which predetermined concentrations of an antigenic substance may be maintained for the calibration of unknown concentrations of the antigenic substance in patient samples. The term "diluent," as used herein, refers to a matrix for dilution of patient samples having concentrations of an antigenic substance which exceed the range of the immunoassay, permitting measurement of the antigenic substance within the immunoassay range.
These matrices are used because unmodified natural matrices, such as serum-based matrices, are rendered unsuitable for use as a result of the instability of PSA upon introduction into such matrices. Specifically, it has been shown that a 30-70% loss of PSA activity occurs within 24 hours after introduction into unmodified human serum-based matrices. Further, this resultant loss of measurable PSA is not limited to human serum since PSA is also unstable upon introduction into bovine and equine serum-based matrices as well.
Because of the dissimilarity of components of such matrices to specimen components, the kinetic patterns on non-specific binding characteristics of artificial matrices may deviate significantly from serum or other body fluids containing, or suspected of containing PSA. As a result, use of these matrices is inherently a substantial limitation to immunoassays for PSA.
Accordingly, to maximize the accuracy and sensitivity of immunoassays for PSA, it is essential that matrices for calibration and sample dilution be as nearly like patient specimens, particularly with respect to non-specific binding characteristics as possible.
Accordingly, there exists a need for means by which PSA may be stabilized in natural matrices, such as serum-based matrices, for use in the quantitative determination of PSA in patient specimens.